Does Enoxaparin treatment have any effects on the placenta in women with unexplained histories of habitual abortion? A case control study

ABSTRACT BACKGROUND: It is very common to offer low molecular weight heparin (LMWH) medications to women with unexplained habitual abortion, to increase the livebirth rate. Although no benefit from LMWH has been clearly demonstrated, examination of the effects of enoxaparin on placental structure is lacking. OBJECTIVE: To assess placental structural changes in pregnancies treated with enoxaparin, compared with controls. DESIGN AND SETTING: Case-control study in an obstetrics and gynecology unit of a tertiary-level university hospital in Turkey. METHODS: Forty patients who had had term pregnancies and live births but also histories of habitual abortion were recruited for this study. Placentas were sampled using a systematic random sampling method. Tissue samples were obtained, embedded and sectioned for routine histological analyses. Hematoxylin and eosin staining was used. Surface area and length estimates from placental components were evaluated by using Image J. Cell proliferation and apoptosis were also assessed via immunohistochemistry. RESULTS: There were no significant differences between the groups regarding maternal age, abortion rate, birth weight or gestational age. Comparison of the enoxaparin and control groups showed that there were no significant differences in terms of surface area and ratios of placental components. We found that Bcl-2 was generally expressed at high levels in the enoxaparin group, while there was no difference in terms of Ki-67 between the groups. CONCLUSIONS: This study demonstrates that enoxaparin did not show any significant effect on the placental structure of cases that had histories of habitual abortion.

Investigation of the protective effect of enoxaparin and ticagrelor pretreatment against ischemia-reperfusion injury in rat lung tissue

SUMMARY OBJECTIVES This study was conducted to reveal the possible protective effects of ticagrelor and enoxaparin pretreatment against ischemia-reperfusion (IR)-induced injury on the lung tissue of a rat model. METHODS Wistar albino rats were randomly divided into 4 groups as follows: group-1 (control-sham), group-2 (control-saline+IR), group-3 (ticagrelor+IR), group-4 (enoxaparin+IR). Before the ischemic period, saline, ticagrelor, and enoxaparin were administered to the 2nd-4th groups, respectively. In these groups, IR injury was induced by clamping the aorta infrarenally for 2 h, followed by 4 h of reperfusion except group-1. After the rats were euthanized, the lungs were processed for histological examinations. Paraffin sections were stained with Haematoxylin&Eosin (H&E) for light microscopic observation. Apoptosis was evaluated by caspase-3 immunoreactivity. Data were statistically analyzed using the SPSS software. RESULTS In the lung sections stained with H&E, a normal histological structure was observed in group-1, whereas disorganized epithelial cells, hemorrhage, and inflammatory cell infiltration were seen in the alveolar wall in group-2. The histologic structure of the treatment groups was better than that of group-2. Caspase-3(+) apoptotic cells were noticeable in sections of group-2 and were lower in the treatment groups. In group-4, caspase-3 immunostaining was lower than in group-3. In group-2, apoptotic cells were significantly higher than in the other groups (p<0.001). CONCLUSION Based on the histological results, we suggested that both therapies ameliorated the detrimental effects of IR. Caspase-3 immunohistochemistry results also revealed that pre-treatment with enoxaparin gave better results in an IR-induced rat injury model. In further studies, other parameters such as ROS and inflammatory gene expressions should be evaluated for accurate results.

RESUMO OBJETIVOS Este estudo foi realizado para revelar os possíveis efeitos protetores do ticagrelor e do pré-tratamento da enoxaparina no tecido pulmonar contra o modelo de lesão induzida por isquemia-reperfusão (IR). MÉTODOS Ratos albinos Wistar foram randomizados e divididos em quatro grupos: grupo 1 (controle-sham), grupo 2 (controle-salina + IR), grupo 3 (ticagrelor + IR), grupo 4 (enoxaparina + IR). Antes do período isquêmico, salina, ticagrelor e enoxaparina foram administrados nos grupos 2-4, respectivamente. Nesses grupos, a lesão de IR foi induzida pelo clampeamento da aorta na região da infrarrenal por duas horas, seguida por quatro horas de reperfusão, exceto no grupo 1. Após a sacrificação, os pulmões foram processados para exames histológicos. Secções de parafina foram coradas com hematoxilina e eosina (H&E) para observação microscópica de luz. A apoptose foi avaliada pela imunorreatividade da caspase-3. Os dados foram analisados estatisticamente pelo programa SPSS. RESULTADOS Nas secções pulmonares coradas com H&E, estrutura histológica normal foi observada no grupo 1, enquanto células epiteliais desorganizadas, hemorragia e infiltração de células inflamatórias foram observadas na parede alveolar no grupo 2. A estrutura histológica dos grupos de tratamento foi melhor que o grupo 2. Células apoptóticas caspase-3 (+) foram notadas em secções do grupo 2, e essas células foram mais baixas nos grupos de tratamento. No grupo 4, a imunocoloração com caspase-3 foi menor que no grupo 3. No grupo 2, as células apoptóticas foram significativamente maiores que nos outros grupos (p<0,001). CONCLUSÃO Com base nos resultados histológicos, sugerimos que ambas as terapias atenuaram os efeitos prejudiciais da RI. Resultados de imuno-histoquímica com caspase-3 também revelaram que o pré-tratamento com enoxaparina proporcionou melhores resultados no modelo de lesão induzida por IR. Em estudos posteriores, outros parâmetros, como ROS e expressões gênicas inflamatórias, devem ser avaliados quanto a resultados precisos.

Caracterización de las potenciales interacciones farmacológicas en pacientes de una unidad de cuidados intensivos en un hospital de tercer nivel de Bogotá / Characterization of potential drug-drug interactions in patients hospitalized in the intensive care unit of a tertiary hospital in Bogotá

Resumen Introducción. Las interacciones farmacológicas ocurren con mayor frecuencia en las unidades de cuidados intensivos que en otros servicios. Sin embargo, en Colombia son pocos los estudios en que se han evaluado en pacientes críticamente enfermos. Objetivos. Caracterizar las potenciales interacciones farmacológicas en las prescripciones de pacientes hospitalizados en una unidad de cuidados intensivos y determinar los factores asociados con su aparición. Materiales y métodos. Se analizó una cohorte retrospectiva de pacientes hospitalizados en una unidad de cuidados intensivos, durante un periodo de siete meses. Las prescripciones diarias se evaluaron en busca de potenciales interacciones farmacológicas mediante el programa Lexicomp™. Se calculó la incidencia de interacciones, se clasificaron según su tipo, gravedad y grado de documentación, y se evaluaron los factores asociados con su aparición mediante regresión logística. Resultados. La proporción de pacientes con por lo menos una interacción fue de 84 %, en tanto que el 87 % presentó más de una interacción; la mediana fue de seis interacciones por paciente. La más frecuente fue entre el fentanilo y el midazolam (23 %). Las interacciones de gravedad y grado de documentación moderados fueron las más frecuentes (77,6 y 52,6 %, respectivamente). El fármaco índice más frecuente fue el midazolam (12 %) y el precipitante más frecuente, el fentanilo (10,6 %). La edad (odds ratio, OR=3,1) y el número de medicamentos (OR=11,8), se asociaron con la aparición de interacciones. Conclusiones. Dada su elevada frecuencia y potencial impacto negativo es importante vigilar sistemáticamente las prescripciones en cuidados intensivos para detectar las interacciones, con el fin de contribuir al uso racional de los medicamentos y a mejorar la calidad de la atención.

Abstract Introduction: Drug-drug interactions occur more frequently in intensive care units than in other services. However, in Colombia, there are few studies on this problem in critically ill patients. Objectives: To characterize potential drug-drug interactions generated from prescriptions during hospitalization in an intensive care unit and to determine factors associated with their onset. Materials and methods: A retrospective cohort was assembled with patients hospitalized in an intensive care unit for a seven-month period. The daily prescription was assessed for potential drugdrug interactions using the Lexicomp® program. We calculated the incidence of interactions, classified them by type, severity, and level of documentation, and evaluated the factors associated with their onset using logistic regression. Results: The proportion of patients with at least one interaction was 84% while 87% had more than one interaction; the median was six interactions per patient. The most frequent was fentanyl and midazolam (23%). Moderate interactions were the most frequent by severity (77.6%) and by documentation (52.6%). The most common index and precipitating drugs were midazolam (12%) and fentanyl (10.6%), respectively. Age (OR=3.1) and the number of drugs (OR=11.8) were associated with the occurrence of interactions. Conclusions: Given their high frequency and potential negative impact, the systematic monitoring of prescriptions in intensive care units to detect interactions is important. Such monitoring contributes to the rational use of medicines and to improve the quality of care.

Doppler velocimetry in fetal rats exposed to enoxaparin and unfractionated heparin (UFH) during pregnancy

Abstract Purpose: To evaluate the effects of enoxaparin and unfractionated heparin (UFH) administered in prophylactic and therapeutic doses on fetal vessels in healthy pregnant Wistar rats, according to Doppler velocimetry measurements. Methods: Fifty animals were assigned to one of five groups: controls (saline), prophylactic and therapeutic enoxaparin (1 and 2 mg/kg/day, respectively), and prophylactic and therapeutic UFH (72 and 400 UI/kg/day, respectively). Uterine horns were examined by ultrasound for identification of live fetuses. A sample of these fetuses underwent Doppler velocimetry. Spectral curves, peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the middle cerebral artery, ductus venosus, and umbilical artery were investigated. Differences were considered statistically significant when p<0.05. Results: No significant differences in PSV, PI, or RI values were observed among the groups. Conclusion: Doppler velocimetry measurements revealed no significant effects of enoxaparin or unfractionated heparin on fetal vessels in pregnant Wistar rats.

Protocolo de prevenção de tromboembolismo venoso em cirurgia plástica: resultados em 2759 pacientes no Instituto Ivo Pitanguy / Venous thromboemboembolism prevention protocol in plastic surgery: results in 2759 patients at the Ivo Pitanguy Institute

Introdução: A embolia pulmonar é a causa de morte mais previsível em pacientes hospitalizados, sendo isso ainda mais prevalente em pacientes cirúrgicos. 200.000 novos casos ocorrem anualmente, com início súbito e geralmente levando à morte nas primeiras 2 horas. Prevenir é, portanto, mais efetivo que tratar a doença estabelecida. Esse estudo objetiva demonstrar a importância e segurança do protocolo de prevenção do tromboembolismo venoso. Métodos: Conduzimos um estudo retrospectivo no período de maio de 2009 a maio de 2011, quando 2759 pacientes foram submetidos à cirurgia plástica no Instituto Ivo Pitanguy. Todos os pacientes foram submetidos ao protocolo de prevenção e avaliados quanto aos fatores de risco para tromboembolismo venoso. A soma desses fatores gerou um escore que determinou a conduta profilática a ser adotada. Resultados: Houve três casos de tromboembolismo venoso (0,1%), sendo 1 de TEP e 2 de TVP. A quimioprofilaxia com enoxaparina administrada aos 3 pacientes de acordo com o protocolo de prevenção. Nossas taxas permaneceram abaixo das encontradas na literatura, com diferença estatisticamente significativa nos numero total de casos (p < 0,0001). Houve 34 casos de hematoma (1,2%), sendo 55,9% em pacientes submetidos à quimioprofilaxia e 44,1% em pacientes que usaram apenas o dispositivo de compressão pneumática intermitente apenas. As taxas totais de hematoma também permaneceram abaixo das encontradas na literatura, também com diferença estatisticamente significativa (p < 0,001). Conclusão: O protocolo de prevenção do tromboembolismo venoso do Instituto Ivo Pitanguy se provou seguro e importante na prevenção dos casos de TEV, com taxas de hematoma abaixo do descrito na literatura.

Introduction: Pulmonary embolism is the most predictable cause of death in hospitalized patients, even more in surgical patients. 200.000 new cases occur annually, with sudden onset and generally leading to death in the first 2 hours. Preventing is most effective than treating stablished disease. This study aims to show the importance and safety of the venous thromboembolism prevention protocol. Methods: We conducted a retrospective study in the period between May 2009 and May 2011 at The Ivo Pitanguy Institute, where 2759 patients underwent plastic surgery (aesthetic and reconstructive). All patients were assessed for predisposing and exposing risk factors for venous thromboembolism and the sum of those factors generated a score determining the prophylactic procedure to be adopted according to the protocol. Results: There were three cases of venous thromboembolism (0.1%): one case of pulmonary embolism and two cases of deep venous thrombosis. Chemoprophylaxis with heparin was administered in the three patients according to the venous thromboembolism prevention protocol. Our rates remained below those found in the literature, with a statistically significant difference in total cases (p < 0.0001). There were 34 cases of hematoma (1.2%): 55.9% in patients submitted to pharmacological prophylaxis with heparin and 44,1% in patients who used sequential compression devices only. The total rates of hematoma also remained below those found in the literature with a statistically significant difference (p < 0,001). Conclusion: The venous thromboembolism prevention protocol of the Ivo Pitanguy Institute proved to be important and safe, preventing the occurrence of venous thromboembolism cases with low rates of hematoma.

Anticoagulação na síndrome coronária aguda / Anticoagulation in acute coronary syndrome

As síndromes coronárias agudas geralmente resultam da instabilização de uma placa aterosclerótica, com subsequente ativação plaquetária e de diversos fatores de coagulação.O tratamento visa aliviar a dor isquêmica, limitar o dano miocárdico e diminuir a mortalidade. Diversos agentes anticoagulantes provaram sua utilidade e novas drogas passarama compor o arsenal terapêutico atual, buscando maior eficácia anti-isquêmica e menores índices de sangramento. Apesar dos avanços, as taxas de mortalidade, reinfarto e reinternação ainda permanecem elevadas. Nessa revisão, sintetizamos as características e aplicabilidade dos anticoagulantes aprovados para o tratamento das síndromes coronárias agudas.

Acute coronary syndromes usually are the result of thedestabilization of atherosclerotic plaque with subsequent plateletand various coagulation factors activation. Treatment aims torelieve ischemic pain, limit myocardial damage and decreasemortality. Several anticoagulants have proven their usefulnessand new drugs compose the therapeutic arsenal, seekinggreater anti-ischemic efficacy and lower rates of bleeding.Despite advances, mortality rates, infarction and hospitalreadmission still remains high. In this review we summarizedthe characteristics and applicability of the anticoagulants thatare approved for the treatment of acute coronary syndromes.

The effect of prophylactic dose of a low molecular weight heparin on skin wound healing of rats / Efeito da dose profilática de heparina de baixo peso molecular na cicatrização de feridas na pele de ratos

PURPOSE: To investigate the effect of prophylactic dose of a low molecular weight heparin, enoxaparin, on skin wound healing of rats. METHODS: Forty rats were used for the study. Rats were randomly assigned to two equal groups. Experimental group received prophylactic dose of enoxaparin. Physiologic saline was administered to the control group. Parameters of wound healing of experimental and control groups were compared. For comparison of the groups in terms of fibrosis, vascularization, inflammation, epithelization, and tensile strength test (Newton). Mann-Whitney-U test was used because variables were categorical data (fibrosis, vascularization, inflammation and epithelization). Differences between groups were analyzed with independent samples t-test (tensile strength). Significance was set at p<0.05. RESULTS: Skin wound of the experimental group presented tensile strength significantly decreased (p<0.001), histopathologic examination revealed a significant (p<0.001) delayed epithelization and decreased in fibrosis, vascularization, inflammation (p<0.001) in the experimental group. CONCLUSION: Enoxaparin delay wound healing by decreased inflammatory cells, fibroblast contents and their products (growth factors), and by promoted hemorrhage.

OBJETIVO: Investigar o efeito de dose profilática da heparina de baixo peso molecular, enoxaparina, na cicatrização de feridas na pele de ratos. MÉTODOS: Quarenta ratos foram utilizados para o estudo. Ratos foram distribuídos aleatoriamente a dois grupos iguais. O grupo experimental recebeu profilática de enoxaparina. Solução salina fisiologica foi administrada ao grupo controle. Foram comparados parâmetros de cicatrização dos grupos experimental e controle.Os grupos foram comparados em termos de fibrose, vascularização, inflamação, epitelização e força tensil (teste de Newton). Foi realizado o teste de Mann-Whitney-U para variáveis com dados categóricos (fibrose, cicatrização, inflamação e epitelização). Diferenças entre os grupos foram analisadas como amostras independentes pelo t-teste (força tensil). Significância foi fixada para p < 0,05. RESULTADOS: A ferida do grupo experimental apresentou força tensil diminuída significativamente (p < 0,001), o exame histopatológico revelou um significativo (p < 0,001) retardo na epitelização e diminuição na fibrose, cicatrização, inflamação (p < 0,001) no grupo experimental. CONCLUSÃO: A enoxaparina retarda a cicatrização da ferida pela diminuição das células inflamatórias, pelo menor conteúdo de fibroblasto e seus produtos (fatores de crescimento) e por promover hemorragia. O grupo experimental foi incluído pela perda significativa da força tênsil no presente estudo.

Duration of late diastolic flow in first trimester in patients with history of recurrent first trimester pregnancy loss in comparison to normal pregnant patients

The purpose of this study is to investigate the correlation between the changes in duration of the absent diastolic flow during first trimester and fetal survival during first trimester pregnancy with and without anti-coagulant treatment. A second objective is to determine the duration and dose of anticoagulant treatment needed to have best outcome in these conditions. A prospective observational study. Al Nahda hospital in cooperation with the maternity hospital in Prince Sultan militaty Hospital, Al Taief, KSA. The study was approved by the committee of study and research in Al Nahdah Hospital. All patients have consented for the plan of care of pregnant women with history of more than previous two consecutive first trimester pregnancy losses with all possible consequences. The study patients are pregnant women with a history of two or more consecutive first trimester pregnancy losses in the form of blighted ovum or sudden first trimester fetal demise. They were studied starting from 6 weeks up to 16 weeks gestaion. The patients were divided into two groups. Group A [n = 12] were managed conservatively with the routine antenatal care without additional anticoagulant treatment and group B [n = 14] were given enoxaparinl 20mg subcutaneously daily starting from the time of positive pregnancy test to end of the study at 16 weeks gestation. A third group of 100 patients with good obstetric history were examined to build up the reference values for the normal progress of the fetal circulation during this period and this group was considered as the control group [group C]. All patients were studied from the time of 6 weeks gestation and up to 16 weeks gestation by Doppler flowmetry to test for the duration of the late diastolic flow in the umbilical arteries. All patients were followed-up starting from 6 weeks gestation till 16 weeks gestations in the period between October 2007 and June 2008. Doppler flowmetry using pulsed. wave color Doppler. In each patient the duration of absent diastolic flow was measured. In group [A], there was persistent longer periods of absent diastolic flow compared to group B and C. In this group four losses happened [2 fetuses were lost at time of 8-10 weeks gestation and 2 patients had blighted ovum]. Patients who were given acetylsalicylic acid and enoxaparine had shorter periods of absent diastolic flow and got a continuous diastolic flow at 13-14 weeks gestation without any losses. The rate of change of the duration of diastolic flow showed that in the B and C groups there is a progressive persistent shortening of the duration of absent diastolic flow by an average rate of 0.0255 seconds per week till 14 weeks when a continous diastolic flow becomes established. On the other hand in group A, the rate of change is very slow [on the average 0.015 seconds per week] up to 16 weeks without a continuous diastolic blood flow. Absent diastolic flow is a normal finding during early pregnancy. Adequate flow without diastolic arrest should be reached by 13-14 weeks gestation. However, patients with history of recurrent first trimester pregnancy loss have longer periods of arrest of diastolic flow. This may be related to imbalance between the coagulation and fibrinolysis in the fetus. This needs further studies to correlate ultrasound findings with coagulation studies during first trimester

Effects of enoxaparin on the healing of abdominal wall in rats: study on breaking strength and histopatology

OBJETIVO: Avaliar a influência da enoxaparina, sobre a cicatrização da parede abdominal. MÉTODOS: Foram utilizados 60 ratos Wistar, distribuídos aleatoriamente em grupo estudo (E) e controle (C). O grupo E recebeu 1 mg/kg de enoxaparina, via subcutânea, do pós-operatório imediato até o 7º dia pós-operatório (DPO); o grupo C doses-volume equivalentes de NaCl 0,9%. Os animais foram submetidos à laparotomia mediana e reoperados no 3º, 7º ou 14º DPO, para ressecção da parede abdominal anterior. A resistência tênsil foi testada e feita avaliação histopatológica. Análise estatística realizada com o teste U de Mann-Whitney, considerando significantes valores de p<0,05. RESULTADOS: A força tênsil de ruptura apresentou mediana de 0,64N para grupo C e de 0,41N para grupo E (p=0,60) no 3º DPO; de 2,27N para grupo C e de 4,32N para grupo E (p=0,01) no 7º DPO; de 5,72N para grupo C e de 6,62N para grupo E (p=0,97) no 14º DPO. Quanto ao estudo histopatológico, os resultados não obtiveram diferenças estatísticas significantes, exceto pela disposição do colágeno no 7º DPO, cujas medianas foram 2 no grupo C e 1 no grupo E (p= 0,007). CONCLUSÃO: Nas condições em que foi realizado o presente estudo, a enoxaparina provocou aumento da força tênsil de ruptura e pior disposição do colágeno no 7º DPO.

Utilidad de la heparina de bajo peso molecular en la sepsis abdominal / The usefulness of low molecular weight heparin in abdominal sepsis

Los fenómenos trombóticos secundarios a procesos sépticos abdominales son causa de una importante postoperatoria. Para su prevención, se ha empleado la heparina regular. Las fracciones de menor peso molecular tienen el mismo efecto, aunque menos efectos secundarios. En el presente trabajo se estudió la utilidad de la enoxaparina, una heparina de bajo peso molecular, para la prevención de los fenómenos trombóticos que ocurren después de un proceso séptico abdominal. Para tal efecto se estudiaron cinco grupos de 10 ratas cada uno. A todos los animales del estudio se les provocó peritonitis fecal. Durante el periodo posoperatorio, al grupo 1 se le administró heparina regular, al grupo 2 enoxaparina, al grupo 3 el antibiótico pefloxacina y a los grupos 4 y 5 la combinación de cada una de las heparinas con pefloxacina. Después de dar muerte a los animales, se realizó estudio de histopatología. Los resultados fueron evaluados con análisis estadístico no paramétrico de Kruskal-Wallis y Mann Whitney. En todas las ratas se produjo sepsis abdominal. El edema intraveolar fue mayor en el grupo de heparina regular comparado con el de enoxaparina con una p de 0.028; el resto de los grupos no tuvo diferencia estadística. Ninguna de las heparinas mostró efecto directo sobre el fenómeno séptico abdominal. En comparación con la heparina regular, la enoxaparina consiguió que las ratas con sepsis tuvieran menor edema intralveolar. No hubo diferencia en cuanto a la prevención de fenómenos trombóticos